Disorders of Megakaryocytes and Platelets

Megakaryocytic hypoplasia is one of the features of congenital or acquired aplastic anemia. Megakaryocytosis and thrombocytosis are associated with acute infections, iron defi ciency, diabetes mellitus, and postsplenectomy status. Postsplenectomy thrombocytosis is typically a transient event. Peripheral destruction of platelets in conditions such as autoimmune-associated thrombocytopenic purpura and drug-induced thrombocytopenia leads to megakaryocytosis secondary to bone marrow compensation. Bone marrow metastasis is a frequent cause of reactive megakaryocytosis due to either the release of TPO-like substances from tumor cells or the increased expression of extracellular matrix (ECM) proteins such as tenascin. Megakaryocytosis is associated with a garden variety of primary bone marrow disorders such as myeloproliferative disorders, myelodysplastic syndromes, and acute megakaryoblastic leukemia. Unlike reactive megakaryocytosis, these conditions are often associated with signifi cant dysplastic changes and arrangement of megakaryocytes in clusters or sheets. Hereditary thrombocythaemia (HT) is an inherited autosomal dominant disorder caused by mutations within the genes encoding TPO or c-Mpl (TPO receptor) genes. A lack or markedly reduced production of megakaryocytes without bone marrow aplasia is rare and has been associated with prolonged administration of prednisone, estrogens, interferon, and chlorothiazide. Chronic alcoholism and certain infectious diseases, such as measles, varicella, infectious mononucleosis, and cytomegalovirus, have been associated with megakaryocytic hypoplasia.